A PHASE III, DOUBLE-BLINDED, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB PLUS COBIMETINIB AND VEMURAFENIB VERSUS PLACEBO PLUS COBIMETINIB AND VEMURAFENIB IN PREVIOUSLY UNTREATED BRAFV600 MUTATION−POSITIVE PATIENTS WITH METASTATIC OR UNRESECTABLE LOCALLY ADVANCED MELANOMA
This study will evaluate the efficacy, safety, and pharmacokinetics of atezolizumab plus cobimetinib plus vemurafenib (atezo + cobi +vem) compared with placebo plus cobimetinib plus vemurafenib (placebo + cobi + vem) in patients with previously untreated, BRAFV600 mutation−positive, metastatic or unresectable locally advanced melanoma. Specific objectives and corresponding endpoints for the study are outlined in the table below.
Atezolizumab 840 mg or placebo will be administered by IV infusion on Days 1 and 15 of Cycle 1 and Days 1 and 15 (every 2 weeks) of subsequent cycles. All patients will receive cobimetinib at a dose of 60 mg (three 20-mg tablets) orally (PO) once daily on Days 1−21 of each 28-day cycle during the run-in and triple combination periods. Cobimetinib should be taken approximately the same time each day, with the morning vemurafenib dose, and no later than 4 hours after the scheduled time. Cobimetinib may be taken with or without a meal. Cobimetinib should be swallowed whole with a glass of water and should not be chewed, cut, or crushed. If a dose of cobimetinib is missed (i.e., not taken within 12 hours after the scheduled dosing time), the patient should resume dosing with the next scheduled dose. Missed or vomited doses will not be made up. Each dose of vemurafenib will consist of four tablets, with patients in Arm A (atezo placebo + cobi + vem) receiving four active tablets and patients in Arm B (atezo + cobi + vem+ vem placebo) receiving three active tablets plus one placebo tablet. All patients will receive vemurafenib at a dose of 960 mg (four 240-mg tablets) PO BID on Days 1−21 of the run-in period. Patients in Arm A will continue to receive vemurafenib at a dose of 960 mg PO BID on Days 22−28 of the run-in period and Days 1−28 of each 28-day cycle during the triple combination period. Patients in Arm B will receive vemurafenib at a dose of 720 mg (three 240-mg tablets) plus vemurafenib placebo (one tablet) PO BID on Days 22−28 of the run-in period and Days 1−28 each 28-day cycle during the triple combination period.
Stadium irresectable IIIc/IV
Age ≥ 18 years
Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locally advanced) melanoma, as defined by the American Joint Committee on Cancer, 7th revised edition
Naïve to prior systemic anti-cancer therapy for melanoma (e.g., chemotherapy, hormonal therapy, targeted therapy, immunotherapy, or other biologic therapies), with the following exceptions:
Adjuvant treatment with interferon, interleukin-2, or vaccine therapies, if discontinued at least 28 days prior to initiation of study treatment is allowed
Documentation of BRAFV600 mutation−positive status in melanoma tumor tissue
Dr. W. Kruit, ErasmusMC Rotterdam